Hitchings Matt D T, Ranzani Otavio T, Torres Mario Sergio Scaramuzzini, de Oliveira Silvano Barbosa, Almiron Maria, Said Rodrigo, Borg Ryan, Schulz Wade L, de Oliveira Roberto Dias, da Silva Patricia Vieira, de Castro Daniel Barros, Sampaio Vanderson de Souza, de Albuquerque Bernardino Cláudio, Ramos Tatyana Costa Amorim, Fraxe Shadia Hussami Hauache, da Costa Cristiano Fernandes, Naveca Felipe Gomes, Siqueira Andre M, de Araújo Wildo Navegantes, Andrews Jason R, Cummings Derek A T, Ko Albert I, Croda Julio
Department of Biology, University of Florida, Gainesville, FL, USA.
Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
Lancet Reg Health Am. 2021 Sep;1:100025. doi: 10.1016/j.lana.2021.100025. Epub 2021 Jul 25.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported.
We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection.
For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate.
Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented.
Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus; Fundação de Vigilância em Saúde do Amazonas.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的伽马变异株于2020年末在玛瑙斯市出现，当时冠状病毒病（COVID-19）大规模复发，并已传播至巴西全国。目前尚无关于在伽马变异株广泛传播地区疫苗有效性的报道。
我们开展了一项配对检测阴性病例对照研究，以评估灭活疫苗科兴新冠疫苗在玛瑙斯医护人员中的有效性。在疫情高峰期，该地区伽马变异株占基因分型SARS-CoV-2样本的86%。我们在至少接种一剂疫苗后进行了早期有效性分析，并对两剂接种方案的有效性进行了分析。主要结局为有症状的SARS-CoV-2感染。
在早期至少一剂和两剂分析中，研究人群分别为居住在玛瑙斯且年龄在18岁及以上的53176名和53153名医护人员，他们拥有关于年龄、居住地和疫苗接种状况的完整信息。在53153名符合两剂分析条件的医护人员中，47170名（89%）接种了至少一剂科兴新冠疫苗，2656人（5%）在2021年1月19日至2021年4月13日期间接受了RT-PCR检测。在3195次RT-PCR检测中，885次（28%）呈阳性。分别为早期分析和两剂分析选择了393对和418对病例对照，根据日历时间、年龄和社区进行配对。在RT-PCR样本采集日期前接种了两剂疫苗的人群中，从第二剂接种到样本采集日期的平均时间为14天（四分位间距7-24天）。在早期分析中，接种至少一剂疫苗与接种第一剂疫苗14天及以后出现有症状SARS-CoV-2感染的几率降低0.50倍相关（调整后的疫苗效力（VE）为49.6%，95%CI为11.3至71.4）。然而，我们估计两剂接种方案在接种第二剂疫苗14天及以后对有症状SARS-CoV-2感染的效力较低（调整后的VE为36.8%，95%CI为-54.9至74.2）。一项发现表明，在接种第一剂疫苗后的0-13天内，接种疫苗的个体比未接种疫苗的个体感染可能性大得多（调整后的比值比为2.11，95%CI为1.36-3.27），这表明未测量的混杂因素导致了疫苗效力估计值的向下偏差。
这项关于科兴新冠疫苗有效性的检测阴性研究的证据存在矛盾，且在这种情况下可能受到偏差影响。接种至少一剂疫苗在伽马变异株流行传播的情况下对有症状的SARS-CoV-2感染显示出有效性。然而，两剂接种方案估计效力较低，这突出表明在实施科兴新冠疫苗接种运动时，仍需维持非药物干预措施。
奥斯瓦尔多·克鲁兹基金会（Fiocruz）；玛瑙斯市卫生局；亚马逊州卫生监督基金会。
